The present invention relates to a flow-through ion exchange medium suitable for chromatography or other forms of separation.
One form of chromatography uses columns packed with a resin typically in the form of granules or particles having adsorptively active surfaces which have been coated with a substance which is functionally active. Preferable shapes for the discrete particle are spheres with regular surfaces. Materials for performing liquid chromatography are known where only thin outer surfaces of the chromatographic support materials are available for active exchange of ions with liquid media. For example, Small, et al. U.S. Pat. No. 4,101,460 describes an ion exchange composition comprising Component A, in insoluble synthetic resin substrate having ion-exchanging sites, at least on its available surface, and having Component B, a finely divided insoluble material, irreversibly attached thereto. Other particulate bed materials with ion exchange layering particles on the outer surface are described in Barretto, U.S. Pat. No. 5,532,279. Barretto describes an ion exchange composition comprising synthetic resins support particles, in dispersant capable of suspending the support particles in an aqueous medium to inhibit or prevent agglomeration, and fine synthetic layering particles. In on embodiment, the complex is formed by contacting a suitable dispersant with monomer in an aqueous solution in which the monomer is insoluble. Under suitable conditions for suspension polymerization, the monomer will polymerize to form resin support particles having a dispersant irreversibly attached to those particles. A number of different embodiments are disclosed for such irreversible attachment.
Frechet, U.S. Pat. No. 5,334,310, describes a continuous liquid chromatographic column which includes a rigid tube and a continuous plug of a macroporous organic polymer within the column extending across the cross-section area of the column. The patent specifically describes a plug containing small pores having diameters less than 200 nm and large pores having diameters greater than about 600 nm. It is generally believed that the larger pores are primarily responsible for permeability and smaller mesopores (e.g., less than 200 nm), which are generally believed to aid in the retention of species to be separated. A variety of polymers are disclosed for use in such continuous plugs or monolithic medium in contrast to the packed bed of particles described above.
U.S. Pat. No. 5,929,214 discloses the preparation of thermally responsive monolithic phases by grafting the pores with thermally responsive polymers or copolymers.
Other monolithic phases used as suppressor packings include radiation grafted materials as set forth in U.S. Pat. No. 6,610,546.
U.S. Pat. No. 5,767,167 discloses the preparation of organic aerogel foams suitable for filtration in concentrating media formed from free radical polymerization of trifunctional or higher functional organic monomers.
Izhizuka & coworkers (Journal of Chromatography A, 797 (1998) 133-137) developed a sol gel process for preparing monolithic phases based on hydrolysis and polycondensation of alkoxysilanes in the presence of water soluble polymers. A bimodal pore structure was observed. One major benefit of a monolithic phase is lower pressure due to a more open pore structure allowing the use of high flow rates without excessive pressure.
In chromatography, the van Deemter equation in terms of HETP is defined as:HETP=A+B/μ+Cμ
μ is the average linear velocity of the mobile phase or eluent and A, B and C are constants. A represents the eddy diffusion which is due to the variation of pathways available through the pores in the column and is independent of the mobile phase velocity, B represents the longitudinal diffusion of the sample components in the mobile phase and C represents the mass transfer. A is characteristic of the column packing and can be decreased with smaller uniform particles and higher packing density. Typically packing columns with smaller particles uniformly is difficult and adapting a monolithic column with the present invention would allow effective reduction in HETP and hence improved separation efficiencies.
The B term is negligible at the high flow rates possible with monolithic columns leading to higher efficiencies. The C term is the mass term transfer and increases with increasing flow rate however several researchers have shown that due to the structure of the monolith this term is not greatly influenced by the higher flow rates.
In ion chromatography the use of latex agglomerated support particles for separations is well accepted. As discussed above, these materials typically consist of a monolayer of small charged colloidal or latex particles that are bound on the surface of larger substrate resin particles. The column capacity and selectivity of the above phases could be optimized based on the choice of the latex and substrate particles. These phases showed higher efficiencies due to faster kinetics and greater permeability relative to standard functionalized or grafted resin phases.
It is difficult to operate the above columns at higher flow rates due to the pressure limitation of these columns. While it is possible to increase the porosity of conventional resins in order to lower the backpressure, the limitation is the lack of mechanical strength of such phases under chromatography conditions.
Therefore it is one objective of the present invention to remove the limitation of high backpressure under high flow conditions and be able to increase separation through put using latex based phases.
The advantage of using a monolithic column is the benefit of lower backpressure allowing the use of higher flow rates and thus leading to higher separation through put. Researchers have demonstrated better mass transport properties of the monolithic phase over conventional resin based phases thus leading to improved separations. Due to the lower pressure drop, steeper flow gradients are possible with a monolithic phase. It was also possible to use longer columns to increase resolution. Monolithic phases however require strict control of conditions during manufacturing. This limitation makes scaleup difficult.
Therefore it is another objective of the present invention to address the limitation of scaleup of monolithic phases.